The human toxicity of marijuana.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
G B Chesher
Publications and source records attributed to G B Chesher.
The human toxicity of marijuana: a critique of a review by Nahas and Latour.
A review entitled "The human toxicity of marijuana" was published in 1992 in the Medical Journal of Australia. The authors claimed that the adverse effects of cannabis use have been trivialized and that the effects are much more serious than earlier reported. We have made a careful study of this review and examined the claims made. We compared the claims of the authors with the information contained in the documents they cited and found that at least 28 of the 35 citations in this article were cited inaccurately. Five of these publications were misquoted, or the findings of the study were not fully reported. Twenty-three citations contained other errors, leaving only six to eight (two citations could not be retrieved because of their obscurity) accurate citations among 35. All of these inaccuracies operate in the direction of finding an adverse effect of marijuana.
Journal Article↗
Science signals a new understanding of marihuana.
Some recent scientific advances in the study of the cannabinoids are outlined. The mode of action of marihuana and the cannabinoids has now been described. They belong to a new class of drug that acts on a hitherto undescribed neuro-physiological system. An endogenous neurotransmitter or neuromodulator for this system has been isolated, identified and named "anandamide". These findings throw new light and imbue new confidence for the future of the therapeutic application of compounds derived from and related to the cannabinoids and anandamide. An outline is also provided of the current knowledge and future potential of cannabinoids in therapeutics. The effect of the current legal classification of the cannabinoids on the research and development of these compounds is discussed.
Journal Article↗
Cimetidine and ranitidine. Lack of effect on the pharmacokinetics of an acute ethanol dose.
The effect of H2-receptor antagonists on alcohol absorption appears to vary, depending on testing conditions and subject population. In this crossover study of cimetidine (400 mg b.i.d.) and ranitidine (150 mg b.i.d.), we evaluate alcohol pharmacokinetics in 10 subjects after ingestion of moderate doses (0.5 g/kg) of ethanol under four challenge conditions: (a) a single dose of placebo prior to alcohol ingestion in the morning, (b) a single dose of H2-antagonist prior to alcohol ingestion in the morning, (c) 14-day chronic dosing with H2-antagonist prior to alcohol ingestion in the evening, and (d) 28-day chronic dosing with H2-antagonist prior to alcohol ingestion in the morning. No significant increases were observed for alcohol in the area under the curve (AUC) or Cmax. Significant decreases in AUC (16 and 13%) were observed following administration of single- and multiple-dose cimetidine, and a significant decrease in Cmax (14%) was observed following a single dose of ranitidine--all given prior to alcohol ingestion in the morning. These results do not support any clinically meaningful effect of H2-antagonists on alcohol absorption following ingestion of a moderate dose of ethanol.
Adult↗
Hazardous amphetamine use: The need to consider dosage.
Explore the source record for details and available documents.
Journal Article↗
Letters to the editor.
Explore the source record for details and available documents.
Journal Article↗
The effects of orally administered delta 9-tetrahydrocannabinol in man on mood and performance measures: a dose-response study.
A dose-response study of the effect of orally administered delta 9-tetrahydrocannabinol (THC) on human mood and skills performance was conducted. Using five dose levels of THC (0, 5, 10, 15, 20 mg) with 16 volunteers per dosage group, mood and performance measures were recorded at five testing occasions, one before and four after drug administration. The slope of the linear regression of performance on the test battery was significant for up to 200 minutes after dosage. That is to say, oral THC, at the doses used, produced significant dose-dependent impairment of performance for a period in excess of three hours. A similar time course for the effect of THC on the subjective assessment of intoxication ('stone') suggested a correlation between drug-induced impairment skills and the effects on mood.
Administration, Oral↗
Patterns of heroin use in the methadone programme in Sydney, 1986-1987.
A study was undertaken to examine patterns of heroin use by clients attending New South Wales Health Department methadone maintenance units in Sydney. The study group included those clients who commenced taking methadone between January 1986 and January 1987 and who remained on individual programmes until December 1987. A total of 16 800 urinalysis results from 346 clients were examined. Data were correlated vertically so as to examine heroin use by all clients beginning with their first dose of methadone. Contrary to expectation, the data indicate that heroin use did not decline as a function of time. The data were further examined within a numerically stable group, which had been sub-classified according to the number of morphine positive urine samples over a period of 12 months. These data indicated the existence of two major groups; those whose continued use of heroin could be described as occasional and another heavy using group. The latter constituted 51% of the study population and contributed almost 90% of the morphine positive urines. The use of urinalysis data to identify the heavy and occasional-user groups could assist in a study to define those factors which could be responsible for the continued use of heroin whilst on a methadone maintenance programme.
Journal Article↗
Controlled availability as an alternative.
Explore the source record for details and available documents.
Journal Article↗
The influence of analgesic drugs in road crashes.
The involvement in road crashes of two classes of drug referred to as analgesics is discussed. Evidence for the effect on traffic safety of each drug group is examined in terms of their behavioural pharmacology and of the available epidemiological data. In the case of the antipyretic analgesics, such as aspirin, there is no evidence to suggest any causative involvement in road crashes. In view of the striking differences in the supply and manner of use of the legal and illegal narcotic analgesics, these are examined separately. The behavioural pharmacology of intravenously administered heroin suggests that any drug induced deficit in driving performance is not due to any effect on psychomotor function, but might be expected from the effect of the drug on mood states. Methadone, as used in treatment schedules for narcotic dependence produces no significant effect on measures of human skills performance. Epidemiological data are contradictory though the suggestion is that the involvement of the narcotic analgesic drugs in road crashes is unlikely to be a source of significant concern. A suggestion is made that a closer examination be undertaken of the involvement in road crashes of the more widely available narcotic drugs codeine and propoxyphene when they are taken together with alcohol.
Accidents, Traffic↗
The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol.
Delta-9-tetrahydrocannabinol (THC), the main psychoactive principle of cannabis, has been shown to attenuate the exhibition of signs of the quasi-morphine withdrawal syndrome in rats. Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect. Cannabidiol was without effect at the dosage levels used. The efficacy of these cannabinoids and the potency differences recorded in this study are in accord with their effects on other behaviours, both in experimental animals and in man. The activity of THC and CBN was not affected by the narcotic antagonist, naloxone.
Animals↗
No evidence for a protracted change in endogenous opioid activity following chronic opiate treatment in mice: parallel recovery of cross tolerance to stress and morphine antinociception.
The involvement of central endogenous opioids in swim-induced antinociception in mice is well documented. The response is attenuated by central or systemic naloxone, displays two-way cross tolerance with morphine and is correlated with apparent occupation of central opiate receptors by endogenous ligands. Swim-induced antinociception was utilised as an in vivo model of endogenous opioid function to investigate a possible protracted functional change in endogenous opioid release or inactivation following chronic opiate treatment. Antinociceptive responses (tail-flick latency) to morphine (4.4 mg/kg, SC) and swimming were determined at various times following chronic methadone (24 days treatment, 102 mg/kg day in drinking water for the last 20 days) and chronic morphine (1 g/kg sustained release) treatment. In both experiments, parallel recovery from cross tolerance was observed for morphine-and swim-induced antinociception. These results were consistent with the view that no protracted functional change in the release or inactivation of endogenous opioids had occurred following chronic opiate treatment.
Animals↗
[3H]Leu-enkephalin binding following chronic swim-stress in mice.
Warm water swimming produces in mice an opiate-like antinociceptive response. Chronic swimming produces tolerance to the antinociceptive response and, depending on the schedule, cross-tolerance with morphine and naloxone intensified withdrawal signs. Low affinity [3H]Leu-enkephalin binding to brain homogenates at low temperature was significantly reduced in acutely swum mice and chronically swum mice whether or not they were swum. Preincubation at 37 degrees C abolished all between-group differences. Results following chronic swimming were similar whether or not the schedule produced morphine cross-tolerance. These results were discussed in terms of the interpretation that reduced binding reflects increase in vivo occupation of opioid binding sites.
Animals↗
Tolerance and cross tolerance with morphine resulting from physiological release of endogenous opiates.
Mice which had been exposed to a chronic schedule of warm water swimming showed the development of a significant tolerance to the antinociceptive response (tail-flick latency) and a significant, two-fold increase in the ED50 of morphine (tail-flick latency and abdominal constriction response). These results suggest the involvement of endogenous opiates during swim stress in mice and are consistent with the hypothesis that during chronic stress the opiate receptors are activated in a manner analogous to the repeated application of exogenous opiates producing tolerance, morphine cross tolerance and (as previously reported) withdrawal-like behaviour.
Animals↗
Physical dependence on physiologically released endogenous opiates.
Mice which had been submitted to a chronic schedule of warm water swimming exhibited a naloxone precipitated withdrawal behaviour which was remarkably similar to that produced in mice following chronic morphine treatment. These results are consistent with the activation of endogenous opiates during swim stress in mice and present the possibility that opiate receptors are activated in a manner analogous to the repeated application of exogenous opiates, producing both tolerance and withdrawal-like behaviour.
Animals↗
Naloxone has no effect on ethanol-induced impairment of psychomotor performance in man.
In a study designed to investigate the effect of naloxone on ethanol-induced performance deficits in man, ethanol (0.75 g/kg) and naloxone (0.4 mg) or saline were administered to 39 volunteers in a double-blind fashion. Psychomotor performance was assessed on a battery of tests (standing steadiness, pursuit rotor, simple and complex reaction times, a speeded number test and the Vienna Determination Apparatus) and blood and breath ethanol concentrations were monitored. Two experiments were performed: in Experiment 1 ethanol was given before naloxone and in Experiment 2 naloxone was administered before ethanol. There were no significant differences in either blood or breath ethanol concentrations at any time between the ethanol + naloxone and ethanol + saline groups in either Experiment 1 or 2. Although ethanol produced a significant decrement on most of the performance measures, naloxone was without effect. There was no suggestion of ethanol impairment being moderated by naloxone, whether it was given before or after ethanol.
Adolescent↗
An analysis of some effects of ethanol on performance in a passive avoidance task.
In a one-trial step-through passive avoidance task, pretraining administration of ethanol was shown to decrease the latencies to step through at both training (day 1) and testing (day 2) for both rats and mice. A detailed analysis of these effects showed that they differed from those reported previously by others. The mechanisms underlying these effects of ethanol were also examined. The decreased day 1 latency to step through seen in rats may have been caused by an ethanol-induced hypermotility. However, ethanol did not increase the locomotor activity of mice, although it also reduced the day 1 latency to step through of this species. In addition, it was found that the ethanol-induced impairment of passive avoidance responding (i.e. the decreased day 2 latency to step through) was not state-dependent and that it was unlikely that it could be explained by a drug-induced impairment of task acquisition, long-term memory formation or memory recall. It also seemed unlikely that the impairment could be explained by an ethanol-induced decrease in shock sensitivity. Other mechanisms which may be involved are discussed.
Animals↗